The goal of this project is to find an agent that would cause a reversal of preneoplasia in epithelial tissue. Retinoids (vitamin A and its analogs) have been the compounds initially being investigated. Emphasis has been placed on determining the metabolic pathways of all-trans-retinyl acetate and all-trans- and 13-cis-retinoic acid. Retinoic acid has been shown to be metabolized to several more polar metabolites both in vitro in a hamster tracheal organ culture system and in vivo in the normal hamster and rat. Several of these metabolites have been identified as the all-trans- and 13-cis- isomers of 4-hydroxy- and 4-oxoretinoic acid. A comparison of the metabolism of all-trans- and 13-cis-retinoic acid demonstrates that these two isomers may to some extent be sharing a common metabolic pathway that includes 13-cis-4-oxoretinoic acid. Although a knowledge of the metabolic pathway of retinoic acid would help to decipher the biochemical mechanism of action of vitamin A in controlling epithelial cell differentiation and would aid in designing analogs of vitamin A that would display biological activity in the reversal of preneoplasia, no metabolites have yet been found that show a biological activity greater than the parent retinoic acid.